Evaluation of PD-L1 Expression and Associated Tumor-Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma

Abstract

Purpose: Programmed death-ligand 1 (PD-L1; also known as CD274 or B7-H1) expression represents a mechanism of immune escape for cancer. Our purpose was to characterize tumor PD-L1 expression and associated T-cell infiltration in primary laryngeal squamous cell carcinomas (SCC). Experimental Design: A well-annotated cohort of 260 operable primary laryngeal SCCs [formalin-fixed paraffin-embedded (FFPE) specimens] was morphologically characterized for stromal tumor-infiltrating lymphocytes (TIL), on hematoxylin/eosin-stained whole sections and for PD-L1 mRNA expression by qRT-PCR in FFPE specimens. For PD-L1 protein expression, automated quantitative protein analysis (AQUA) was applied on tissue microarrays consisting of two cores from these tumors. In addition, PD-L1 mRNA expression in fresh-frozen tumors and normal adjacent tissue specimens was assessed in a second independent cohort of 89 patients with primary laryngeal SCC. Results: PD-L1 mRNA levels were upregulated in tumors compared with surrounding normal tissue (P = 0.009). TILs density correlated with tumor PD-L1 AQUA levels (P = 0.021). Both high TILs density and high PD-L1 AQUA levels were significantly associated with superior disease-free survival (DFS; TILs: P = 0.009 and PD-L1: P = 0.044) and overall survival (OS; TILs: P = 0.015 and PD-L1: P = 0.059) of the patients and retained significance in multivariate analysis. Conclusions: Increased TILs density and PD-L1 levels are associated with better outcome in laryngeal squamous cell cancer. Assessment of TILs and PD-L1 expression could be useful to predict response to immune checkpoint inhibitors. Clin Cancer Res; 22(3); 704–13. ©2015 AACR.

Tumor PD-L1 expression is correlated with increased TILs and poor prognosis in penile squamous cell carcinoma

“…Several researches also described similar association. 23,31,32 This correlation was in accordance with the previous finding that IFNg, expressed by activated CD8 C T cells, can induce PD-L1 expression in the surrounding tumor cells. 33 Moreover, seven patients (Table 2) with absent or focal TILs still presented PD-L1 positivity.…”

PD-1 Expression in Head and Neck Squamous Cell Carcinomas Derives Primarily from Functionally Anergic CD4+ TILs in the Presence of PD-L1+ TAMs

“…In contrast, PD-L1 expression was correlated with improved survival in laryngeal squamous cell carcinomas (17). In another study, PD-L1 expression did not demonstrate an overall survival benefit in patients with cervical cancer (N=115 patients) (18).…”

Assessing Tumor-Infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method from the International Immuno-Oncology Biomarkers Working Group: Part 2: TILs in Melanoma, Gastrointestinal Tract Carcinomas, Non–Small Cell Lung Carcinoma and Mesothelioma, Endometrial and Ovarian Carcinomas, Squamous Cell Carcinoma of the Head and Neck, Genitourinary Carcinomas, and Primary Brain Tumors

“…Similar favorable findings were seen with increased intra-tumoral or stromal CD8 + cells [240], while increased numbers of FOXP3 + T regs may have detrimental effects oral cavity squamous cell carcinoma outcome [241]. Vassilakopoulou et al and Wang et al applied the consensus TILs scoring guidelines from the International Immuno-Oncology Biomarkers Working Group [1] to laryngeal squamous cell carcinoma, and both studies found that the sTILs score was an independent prognostic factor for disease free and overall survival [242,243]. …”